Synthesis and in vitro evaluation of the anticancer potential of new aminoalkanol derivatives of xanthone
| Autor: | Anna Galilejczyk, Ilona Bednarek, Henryk Marona, Sabina Gałka, Daniel Sypniewski, Natalia Szkaradek, Anna M. Waszkielewicz, Agnieszka Gunia-Krzyżak |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Gelatinases Xanthones Antineoplastic Agents Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Xanthone Tumor Cells Cultured Humans Zymography Cytotoxicity Cell Proliferation Pharmacology Dose-Response Relationship Drug Amino Alcohols In vitro 030104 developmental biology Biochemistry chemistry Cell culture Apoptosis 030220 oncology & carcinogenesis Cancer cell Molecular Medicine Drug Screening Assays Antitumor Reactive Oxygen Species |
| Popis: | A series of 15 derivatives of xanthone were synthesized and evaluated for the anticancer activity. The structure of the tested compounds was diversified to establish structureactivity relationships. The following evaluations were carried out: cytotoxicity-proliferation tests, apoptosis detection, expression of apoptosis and proliferation-related genes, expression and activity of gelatinases A and B, wound migration assays, and cell adhesion to MatrigelTMcoated plates. Four compounds (7, 12, 13 and 15) displayed direct cytotoxicity at micromolar concentrations toward the studied cell lines. They also significantly affected the expression of proliferationapoptosis markers, and 13 demonstrated as strong influence as α-mangostin, that served as a natural standard in our study. These four compounds also decreased the expression and activity of gelatinases, and inhibited the migration-motility potential of cancer cells. The influence of compounds 7 and 12 on MMPs mRNA levels even exceeded the activity of α-mangostin and shRNA-mediated silencing; zymography revealed that 7, 13 and 15 were as equally active as α-mangostin, despite their higher IC50 values. The highest activity to inhibit motility and migration of cancer cells was demonstrated by 7, 12, 15, and by α-mangostin; and this was almost equal to shRNA-mediated silencing. Structural features predetermining compound activity were: substitution at position C4 instead of C2, and presence of a chlorine atom and allyl moiety. These results indicate that synthesis of aminoalkanol derivatives of xanthone may lead to successful establishment of new potential anticancer chemicals. |
| Databáze: | OpenAIRE |
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